This proposal represents an approach to the mechanism by which chronic coronary heart disease leads to lethal arrhythmias and sudden death. Three Projects are included: I. A study of the chemical nature of a Ca2 ion channel in sarcoplasmic reticulum vesicles; II. A study of the control of cation fluxes in mammalian heart cells in tissue culture; and III. A study of the influence of membrane potential in SR vesicles on the Ca-permeability characteristics. In these projects we plan to examine the effects of high-energy phosphates, pH and catecholamines. In the SR, the latter studies will include cardiac vesicles phosphorylated by a cyclic AMP-dependent protein kinase. The actions of antiarrhythmic drugs will be examined in these projects in an effort to define the most appropriate means to reverse or ameliorate the abnormalities that would be expected, in the ischemic heart, to lead to lethal arrhythmias and sudden cardiac death.